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Histone demethylase

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https://www.readbyqxmd.com/read/28073943/kdm4b-jmjd2b-is-a-p53-target-gene-that-modulates-the-amplitude-of-p53-response-after-dna-damage
#1
Laura Castellini, Eui Jung Moon, Olga V Razorenova, Adam J Krieg, Rie von Eyben, Amato J Giaccia
The p53 tumor suppressor protein plays a critical role in orchestrating the genomic response to various stress signals by acting as a master transcriptional regulator. Differential gene activity is controlled by transcription factors but also dependent on the underlying chromatin structure, especially on covalent histone modifications. After screening different histone lysine methyltransferases and demethylases, we identified JMJD2B/KDM4B as a p53-inducible gene in response to DNA damage. p53 directly regulates JMJD2B gene expression by binding to a canonical p53-consensus motif in the JMJD2B promoter...
January 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28067305/gomisin-n-inhibits-adipogenesis-and-prevents-high-fat-diet-induced-obesity
#2
Min-Kyung Jang, Ye-Rang Yun, Ji-Hyun Kim, Mi-Hee Park, Myeong Ho Jung
Gomisin N (GN) is a physiological lignan derived from Schisandra chinensis. In the present study, we investigated the inhibitory effects of GN on differentiation of 3T3-L1 preadipocytes and the anti-obesity effects of GN in high-fat diet (HFD)-induced obese mice. Incubation with GN significantly inhibited the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner. This inhibitory effect primarily occurred at an early adipogenic stage through impairment of mitotic clonal expansion (MCE) caused by cell cycle arrest at the G1/S phase transition...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28064082/novel-flavonol-analogues-as-potential-inhibitors-of-jmjd3-histone-demethylase-a-study-based-on-molecular-modelling
#3
Sanchari Basu Mallik, Aravinda Pai, Rekha R Shenoy, B S Jayashree
Epigenetic modulation of gene expression has drawn enormous attention among researchers globally in the present scenario. Since their discovery, Jmj-C histone demethylases were identified as useful markers in understanding the role of epigenetics in inflammatory conditions and in cancer as well. This has created arousal of interest in search of suitable candidates. Potential inhibitors from various other scaffolds such as hydroxyquinolines, hydroxamic acids and triazolopyridines have already been identified and reported...
December 13, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28060835/histone-h3k9-demethylase-jmjd2b-activates-adipogenesis-by-regulating-h3k9-methylation-on-ppar%C3%AE-and-c-ebp%C3%AE-during-adipogenesis
#4
Min-Kyung Jang, Ji-Hyun Kim, Myeong Ho Jung
Previous studies have shown that tri- or di-methylation of histone H3 at lysine 9 (H3K9me3/me2) on the promoter of the peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) contribute to the repression of PPARγ and C/EBPα and inhibition of adipogenesis in 3T3-L1 preadipocytes. The balance of histone methylation is regulated by histone methyltransferases and demethylases. However, it is poorly understood which demethylases are responsible for removing H3K9me3/me2 on the promoter of PPARγ and C/EBPα...
2017: PloS One
https://www.readbyqxmd.com/read/28053115/cytosine-methylation-at-cpcpg-sites-triggers-accumulation-of-non-cpg-methylation-in-gene-bodies
#5
Nicolae Radu Zabet, Marco Catoni, Filippo Prischi, Jerzy Paszkowski
Methylation of cytosine is an epigenetic mark involved in the regulation of transcription, usually associated with transcriptional repression. In mammals, methylated cytosines are found predominantly in CpGs but in plants non-CpG methylation (in the CpHpG or CpHpH contexts, where H is A, C or T) is also present and is associated with the transcriptional silencing of transposable elements. In addition, CpG methylation is found in coding regions of active genes. In the absence of the demethylase of lysine 9 of histone 3 (IBM1), a subset of body-methylated genes acquires non-CpG methylation...
January 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28051298/the-activity-of-jmjc-histone-lysine-demethylase-kdm4a-is-highly-sensitive-to-oxygen-concentrations
#6
Rebecca L Hancock, Norma Masson, Kate Dunne, Emily Flashman, Akane Kawamura
The JmjC-histone lysine demethylases (KDMs) are epigenetic regulators involved in the removal of methyl groups from post-translationally modified lysyl residues within the histone tails, modulating gene transcription. These enzymes require molecular oxygen for catalytic activity and, as 2-oxoglutarate (2OG) dependent oxygenases, are related to the cellular oxygen sensing HIF hydroxylases PHD2 and FIH. Recent studies have indicated that the activity of some KDMs, including the pseudogene-encoded KDM4E, may be sensitive to changing oxygen concentrations...
January 4, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28049654/histone-lysine-demethylase-inhibitors
#7
REVIEW
Ashwini Jambhekar, Jamie N Anastas, Yang Shi
The dynamic regulation of covalent modifications to histones is essential for maintaining genomic integrity and cell identity and is often compromised in cancer. Aberrant expression of histone lysine demethylases has been documented in many types of blood and solid tumors, and thus demethylases represent promising therapeutic targets. Recent advances in high-throughput chemical screening, structure-based drug design, and structure-activity relationship studies have improved both the specificity and the in vivo efficacy of demethylase inhibitors...
January 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28041878/epigenetic-modifiers-facilitate-induction-and-pluripotency-of-porcine-ipscs
#8
Jian Mao, Qian Zhang, Wei Deng, Hua Wang, Kai Liu, Haifeng Fu, Qiang Zhao, Xumin Wang, Lin Liu
Inadequate silencing of exogenous genes represents a major obstacle to complete epigenetic reprogramming of porcine-induced pluripotent stem cells (piPSCs) by conventional pluripotency transcription factors (OSKM). We tested the hypothesis that epigenetic modification by active DNA or histone demethylation or by inhibition of histone deacetylase would enhance reprogramming and exogenous gene silencing in piPSCs. piPSCs induced by OSKM in combination with epigenetic factors, specifically Ten-Eleven Translocation (Tet1 or Tet3) or lysine (K)-specific demethylase 3A (Kdm3a), expressed higher levels of Rex1 and other genes representing naive state and exhibited more open chromatin status, compared with those of OSKM controls...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28036257/epigenetic-therapy-in-urologic-cancers-an-update-on-clinical-trials
#9
REVIEW
Inês Faleiro, Ricardo Leão, Alexandra Binnie, Ramon Andrade de Mello, Ana-Teresa Maia, Pedro Castelo-Branco
Epigenetic dysregulation is one of many factors that contribute to cancer development and progression. Numerous epigenetic alterations have been identified in urologic cancers including histone modifications, DNA methylation changes, and microRNA expression. Since these changes are reversible, efforts are being made to develop epigenetic drugs that restore the normal epigenetic patterns of cells, and many clinical trials are already underway to test their clinical potential. In this review we analyze multiple clinical trials (n=51) that test the efficacy of these drugs in patients with urologic cancers...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031467/maternal-sall4-is-indispensable-for-epigenetic-maturation-of-mouse-oocytes
#10
Kai Xu, Xia Chen, Hui Yang, Yiwen Xu, Yuanlin He, Chenfei Wang, Hua Huang, Baodong Liu, Wenqiang Liu, Jingyi Li, Xiaochen Kou, Yanhong Zhao, Kun Zhao, Linfeng Zhang, Zhenzhen Hou, Hong Wang, Hailin Wang, Jing Li, Hengyu Fan, Fengchao Wang, Yawei Gao, Yong Zhang, Jiayu Chen, Shaorong Gao
Splat-like 4 (Sall4) plays important roles in maintaining pluripotency of embryonic stem cells and in various developmental processes. Here, we find that Sall4 is highly expressed in oocytes and early embryos. To investigate the roles of SALL4 in oogenesis, we generated Sall4 maternal specific knockout mice by using CRISPR/Cas9 system. And we find that the maternal deletion of Sall4 causes developmental arrest of oocytes at germinal vesicle stage with non-surrounded nucleus and the subsequent meiosis resumption is prohibited...
December 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28029651/the-pseudogene-duxap10-promotes-an-aggressive-phenotype-through-binding-with-lsd1-and-repressing-lats2-and-rrad-in-non-small-cell-lung-cancer
#11
Chen-Chen Wei, Feng-Qi Nie, Li-Li Jiang, Qin-Nan Chen, Zhen-Yao Chen, Xin Chen, Xuan Pan, Zhi-Li Liu, Bin-Bin Lu, Zhao-Xia Wang
Pseudogenes have been considered as non-functional transcriptional relics of human genomic for long time. However, recent studies revealed that they play a plethora of roles in diverse physiological and pathological processes, especially in cancer, and many pseudogenes are transcribed into long noncoding RNAs and emerging as a novel class of lncRNAs. However, the biological roles and underlying mechanism of pseudogenes in the pathogenesis of non small cell lung cancer are still incompletely elucidated. This study identifies a putative oncogenic pseudogene DUXAP10 in NSCLC, which is located in 14q11...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28011933/epigenetic-and-transcriptional-regulation-of-irak-m-expression-in-macrophages
#12
Konstantina Lyroni, Andreas Patsalos, Maria G Daskalaki, Christina Doxaki, Birte Soennichsen, Mike Helms, Ioannis Liapis, Vassiliki Zacharioudaki, Sotirios C Kampranis, Christos Tsatsanis
During macrophage activation, expression of IL-1R-associated kinase (IRAK)-M is induced to suppress TLR-mediated responses and is a hallmark of endotoxin tolerance. Endotoxin tolerance requires tight regulation of genes occurring at the transcriptional and epigenetic levels. To identify novel regulators of IRAK-M, we used RAW 264.7 macrophages and performed a targeted RNA interference screen of genes encoding chromatin-modifying enzymes, signaling molecules, and transcription factors involved in macrophage activation...
December 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27994610/genome-wide-analysis-of-soybean-jmjc-domain-containing-proteins-suggests-evolutionary-conservation-following-whole-genome-duplication
#13
Yapeng Han, Xiangyong Li, Lin Cheng, Yanchun Liu, Hui Wang, Danxia Ke, Hongyu Yuan, Liangsheng Zhang, Lei Wang
Histone modifications, such as methylation and demethylation, play an important role in regulating chromatin structure and gene expression. The JmjC domain-containing proteins, an important family of histone lysine demethylases (KDMs), play a key role in maintaining homeostasis of histone methylation in vivo. In this study, we performed a comprehensive analysis of the jumonji C (JmjC) gene family in the soybean genome and identified 48 JmjC genes (GmJMJs) distributed unevenly across 18 chromosomes. Phylogenetic analysis showed that these JmjC domain-containing genes can be divided into eight groups...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27992400/the-histone-demethylase-utx-regulates-the-lineage-specific-epigenetic-program-of-invariant-natural-killer-t-cells
#14
Semir Beyaz, Ji Hyung Kim, Luca Pinello, Michael E Xifaras, Yu Hu, Jialiang Huang, Marc A Kerenyi, Partha P Das, R Anthony Barnitz, Aurelie Herault, Rizkullah Dogum, W Nicholas Haining, Ömer H Yilmaz, Emmanuelle Passegue, Guo-Cheng Yuan, Stuart H Orkin, Florian Winau
Invariant natural killer T cells (iNKT cells) are innate-like lymphocytes that protect against infection, autoimmune disease and cancer. However, little is known about the epigenetic regulation of iNKT cell development. Here we found that the H3K27me3 histone demethylase UTX was an essential cell-intrinsic factor that controlled an iNKT-cell lineage-specific gene-expression program and epigenetic landscape in a demethylase-activity-dependent manner. UTX-deficient iNKT cells exhibited impaired expression of iNKT cell signature genes due to a decrease in activation-associated H3K4me3 marks and an increase in repressive H3K27me3 marks within the promoters occupied by UTX...
December 19, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27991916/the-hif-phf8-ar-axis-promotes-prostate-cancer-progression
#15
D Tong, Q Liu, G Liu, W Yuan, L Wang, Y Guo, W Lan, D Zhang, S Dong, Y Wang, H Xiao, J Mu, C Mao, J Wong, J Jiang
Recent studies provide strong evidence that the androgen receptor (AR) signaling pathway remains active in castration-resistant prostate cancer (CRPC). However, the underlying mechanisms are not well understood. In this study, we demonstrate that plant homeo domain finger protein 8 (PHF8 )interacts with and functions as an essential histone demethylase activity-dependent AR coactivator. Furthermore, we demonstrate that the expression of PHF8 is induced by hypoxia in various prostate cancer cell lines. Knockdown of either hypoxia-inducible factor HIF2α or HIF1α almost completely abolished hypoxia-induced PHF8 expression...
December 19, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27989769/adaptive-chromatin-remodeling-drives-glioblastoma-stem-cell-plasticity-and-drug-tolerance
#16
Brian B Liau, Cem Sievers, Laura K Donohue, Shawn M Gillespie, William A Flavahan, Tyler E Miller, Andrew S Venteicher, Christine H Hebert, Christopher D Carey, Scott J Rodig, Sarah J Shareef, Fadi J Najm, Peter van Galen, Hiroaki Wakimoto, Daniel P Cahill, Jeremy N Rich, Jon C Aster, Mario L Suvà, Anoop P Patel, Bradley E Bernstein
Glioblastoma, the most common and aggressive malignant brain tumor, is propagated by stem-like cancer cells refractory to existing therapies. Understanding the molecular mechanisms that control glioblastoma stem cell (GSC) proliferation and drug resistance may reveal opportunities for therapeutic interventions. Here we show that GSCs can reversibly transition to a slow-cycling, persistent state in response to targeted kinase inhibitors. In this state, GSCs upregulate primitive developmental programs and are dependent upon Notch signaling...
December 2, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27983866/minireview-therapeutic-implications-of-epigenetic-signaling-in-breast-cancer
#17
Tae Gyu Oh, Shu-Ching M Wang, George E O Muscat
Breast cancer is a heterogeneous disease and its complexity has hindered the development of efficacious treatments targeting all breast cancer subtypes. Many studies have linked the diversity of breast carcinogenesis and metastasis to aberrant epigenetic signaling and control. Here, we focus on the current state of the discipline and review the major epigenetic enzymes controlling chromatin structure and function in the context of breast cancer, including i) DNA methyltransferases, ii) lysine methyltransferases and demethylases, iii) protein arginine methyltransferases, iv) histone acetyltransferases and deacetylases...
December 16, 2016: Endocrinology
https://www.readbyqxmd.com/read/27983522/different-expression-patterns-of-histone-h3k27-demethylases-in-renal-cell-carcinoma-and-bladder-cancer
#18
Zehui Hong, Hui Li, Lili Li, Weilong Wang, Ting Xu
OBJECTIVE: UTX and JMJD3 are recently identified histone H3 lysine 27 (H3K27) demethylases. Many studies have shown aberrant H3K27 trimethylation (H3K27me3) levels widely exist in multiple cancers, and that altered H3K27me3 levels are correlated with tumorigenesis and tumor progression. To investigate expression patterns of UTX and JMJD3 genes in renal cell carcinoma (RCC) and bladder cancer and the relationship between gene expression and tumor development. MATERIAL AND METHODS: Samples were collected from 35 patients with RCC and 21 patients with bladder cancer and qRT-PCR was performed...
December 9, 2016: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/27978997/corrigendum-to-kdm4c-a-h3k9me3-histone-demethylase-is-involved-in-the-maintenance-of-human-escc-initiating-cells-by-epigenetically-enhancing-sox2-expression-neoplasia-18-2016-594-609
#19
Xiang Yuan, Jinyu Kong, Zhikun Ma, Na Li, Ruinuo Jia, Yiwen Liu, Fuyou Zhou, Qimin Zhan, Gang Liu, Shegan Gao
No abstract text is available yet for this article.
December 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27977115/lsd1-substrate-binding-and-gene-expression-are-affected-by-hdac1-mediated-deacetylation
#20
Dhanusha A Nalawansha, Mary Kay H Pflum
Lysine Specific Demethylase 1 (LSD1) catalyzes the demethylation of histone 3 to regulate gene expression. With a fundamental role in gene regulation, LSD1 is involved in multiple cellular processes, including embryonic development, cell proliferation, and metastasis. Significantly, LSD1 is overexpressed in multiple cancers and has emerged as a potential anticancer drug target. LSD1 is typically found in association with another epigenetic enzyme, histone deacetylase (HDAC). HDAC and LSD1 inhibitor compounds have been tested as combination anticancer agents...
December 15, 2016: ACS Chemical Biology
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